Reaction Steps
A stirred solution of the above 5-(tert-butyloxycarbonylamino)-1-(chloromethyl)-3-trifluoroacetyl-1,2-dihydro-3H-benz[e]indole (100 mg, 0.23 mmol) in N-methylpyrrolidone (2.5 mL) was treated dropwise at 20° C. with a solution of Cs2CO3 (650 mg) in water (1.5 mL). the mixture was stirred for a further 45 min at 20° C. then diluted with water (20 mL) and extracted with benzene (2×15 mL). The combined organic extracts were washed with water (2×), dried (Na2SO4) and concentrated under reduced pressure below 30° C. The residue was dissolved in pyridine (2 mL), cooled to -5° C. and treated with (E)-4-methoxycinnamoyl chloride (46 mg, 0.23 mmol) followed by DMAP (15 mg). The mixture was stirred for a further 30 min at 20° C., then diluted with KHCO3 solution. The precipitated solid was collected, washed with water, dried and chromatographed on silica gel. Elution with CH2Cl2 /EtOAc gave the crude product which was recrystallised from CH2Cl2 /petroleum either to give 5-(tert-butyloxycarbonylamino)-1-(chloromethyl)-3-[(E)-4-methoxycinnamoyl]-1,2-dihydro-3H-benz[e]indole (55 mg, 48%), mp 185-185.5° C. 1H NMR [(CD3)2SO] δ 9.28 (br s, 1 H, NH), 8.64 (br s, 1 H, H-4), 8.01 (d, J=8.1 Hz, 1 H, H-6), 7.92 (d, J=8.3 Hz, 1 H, H-9), 7.78 (d, J=8.6 Hz, 2 H, H-2',6'), 7.66 (d, J=15.3 Hz, 1 H, PhCH=CH), 7.54 (t, J=7.6 Hz, 1 H, H-8), 7.42 (t, J=7.7 Hz, 1 H, H-7), 7.10 (d, J=15.2 Hz, 1 H, PhCH=CH), 7.01 (d, J=8.7 Hz, 2 H, H-3',5'), 4.60-4.44 (m, 2 H, H-2), 4.41-4.28 (m, 1 H, H-1), 4.02 (dd, J=11.1, 3.0 Hz, 1 H, CHHCl), 3.92 (dd, J=11.1, 7.2 Hz, 1 H, CHHCl), 3.82 (s, 3 H, OCH3), 1.51 (s, 9 H, C(CH3)3).
